|| UPDATED TASK DESCRIPTION/PROJECT RATIONALE AUGUST 2016:
This new task is proposed as a directed/solicited study that will engage multiple external and/or international collaborators. Specific rational for the directed portion of the study is as follows:
Validated assays - requirement for technical homology: Some of the same measurements previously demonstrated to be dysregulated during long-duration spaceflight should be continued during the new study. It is important to correlate demonstrated areas of dysregulation in adaptive or viral parameters with new areas of investigation in the same individual subjects. Otherwise the result is separate data sets among which it is impossible to perform correlative analysis to determine mechanistic interactions. Many of these assays, as implemented during the Integrated Immune flight study, were developed and fully validated (and published) at Johnson Space Center (JSC). To solicit for assays would introduce additional and unnecessary cost and delay, as well as invite technical differences that could have a negative effect on data correlations.
Validated sample processing protocols: For implementation of Integrated Immune, it was necessary to create and validate sample processing protocols (sample stability, storage conditions, methods to stain/fix/preserve, elimination of autofluorescence, etc.). In most cases, these requirements are unnecessary for terrestrial laboratories that do not deal with operational constraints. Terrestrial laboratories do not routinely analyze, nor do they even accept, aged samples. For example, sample preservation (cell, nucleic acid, culture products) must be stabilized to support IP participation.
Requirement for established collaborations: We anticipate that validate assays from international partner flight studies would be necessary for the success of this proposal. The NASA JSC investigators have established both flight and ground collaborations with other US and International Partner immunologists. Rather than repeat flight studies sequentially, it is desirable to collaborate for the planned studies, so that all relevant in-flight assays may be performed. Examples include assays from the Salivary Markers, Immuno, MoCISS flight studies, as well as the CHOICE and NEEMO (NASA Extreme Environment Mission Operations project) analog studies.
Implementation Aspects: For a complicated medical study with unique sampling constraints, the success of the Integrated Immune flight study has demonstrated the advantages of an in-house investigator component for study success. This is relevant to crew ICB, crew training, sample processing and distribution, and central coordination of sampling, sample sharing, maintenance of banked samples, sample storage for batch analysis, facilitation of data coordination for interpretative purposes, data coordination for report generation, interdisciplinary aspects (established linkages with Nutrition, Bone, Cardio disciplines, etc.), and interface with JSC flight surgeons, JSC data archives. Examples include Integrated Immune, where immune data are being coordinated with crew sleep/wake cycles and circadian misalignment, and the planning for the Salivary Markers flight study.
Operational constraints-- Requirement for integrated and Immediate Sample Processing: The solicited aspects for this study will essentially be a very complicated sample sharing activity. All samples, including in-flight samples, must be processed at JSC, as JSC is the location where all BDC samples are collected, and where all in-flight samples return. In-flight samples will be at the end of their viability lifespan, by the time they are collected on-orbit, through hatch closure, deorbit, Soyuz return, and direct aircraft return to JSC. At this time, sample processing must occur without delay. Often, due to short (or otherwise sub optimal samples) real time judgment calls must be made to allow the maximal scientific return. We propose that to ensure mission success, the experienced JSC (directed) investigator team carry the integration responsibility for the entire team. The JSC staff has extensive experience regarding the integration required to support multiple immune investigators. For Integrated Immune, a study that also consisted of in-house and external collaborators (Mercer University, Microgen Laboratories, etc.), our suggested processing/implementation design worked well. For human subject samples, sampling volumes must be minimal, yet maximal assays must be generated on that product. JSC staff has processed ESA (European Space Agency) samples for both the NEEMO and Antarctica studies, and are knowledgeable regarding successfully integrating multiple IP studies on minimal sample. Outside investigators do not routinely work within this constraints.
Cost and efficiency: Given the above requirements for assays, integration, sample processing, and that these unique and validated assays and sample processing protocols are in-place at JSC, it would introduce significant additional cost to ‘train’ an external lab perform these assays to the same fidelity.
TASK DESCRIPTION NOVEMBER 2014: Some aspects of adaptive cellular immunity have been characterized during spaceflight, while many other areas of immunity (humoral, innate, cell specific functional, etc.) have not. The objective of this project is to characterize multiple diverse facets of immunoregulation during long-duration spaceflight. We hypothesize that while aspects of adaptive immune function are depressed during spaceflight, aspects of humoral or innate immune function may be unaltered or even sensitized. This would explain the observed reactivation of latent herpesviruses in astronauts, and also the elevated incidence of skin rashes and hypersensitivity reactions during International Space Station (ISS) missions. If the hypothesis is validated, it would be an important consideration for any future immunology countermeasures. For example, one would not give an immune ‘booster’ to address T cell function in a crewmember, if it might potentially worsen on-orbit skin rashes or allergy symptoms. We further hypothesize that there is a widely disparate post-landing recovery for various aspects of immune dysregulation following flight. Previous data have demonstrated that, surprisingly, ISS astronauts maintain shedding of latent herpesviruses at least to R+30. This study will fully characterize all relevant immune dysregulation through a post-mission recovery.
The primary purpose of the study is to determine both acute and chronic alterations in crewmember immunobiology (both innate + adaptive parameters) in conjunction with relevant parameters from other disciplines (nutritional, radiation, virology, host-pathogen, stress, etc.). Parameters will be examined longitudinally in Astronauts before, during, and following spaceflight. Post-flight assessments will be extended to determine the timecourse for full recovery of any dysregulated parameters. Specific scientific aims are as follows:
1. Longitudinally examine the effect of spaceflight on previously uninvestigated aspects of immunobiology including leukocyte distribution, various aspects of innate cellular function. Examined concurrently will be several previously validated assays of adaptive cellular distribution and function, to correlate within crewmembers both innate and adaptive immune dysregulation.
2. Examine the relationship in astronauts between immune function and various markers of in-vivo immune-physiological status, including plasma, salivary and urinary markers of stress, antimicrobial activity, and latent viral reactivation. Various solicited parameters are planned to augment this specific aim, including proteomics and/or genomics.
3. Correlate findings of immune status with astronaut environmental, human, and stress factors such as sleep/wake data, crew work schedules, surveys of in-flight symptomology and/or medication use (voluntary), vehicle docking/undocking, extravehicular activity (EVA), etc. This correlative work should allow conclusions regarding environmental factors, which may potentially be modulated, on immune status.
4. Incorporate a final data analysis into specific conclusions regarding the immunobiology of spaceflight and conclusions regarding the necessity, lack thereof, or targeted aspects of, immune countermeasures for spaceflight. Develop a refined monitoring strategy encompassing innate immunity, adaptive immunity, and relevant parameters from other disciplines, which will be appropriate to validate countermeasures.